Should Kratom Use Be Legal?

Thailand is considering legalizing kratom as a safer alternative
for meth addicts, and U.S. researchers are studying its potential
to help opiate abusers kick the habit without withdrawal side
effects. Is that a good thing?

The leaves of the herb kratom (Mitragyna speciosa), a native of
Southeast Asia in the coffee family, are used to relieve pain and
improve mood as an opiate substitute and stimulant. The herb is
also combined with cough syrup to make a popular beverage in
Thailand called “4×100.” Because of its psychoactive properties,
however, kratom is illegal in Thailand, Australia, Myanmar (Burma)
and Malaysia. The U.S. Drug Enforcement Administration lists kratom
as a “drug of concern” because of its abuse potential, stating it
has no legitimate medical use. The state of Indiana has banned
kratom consumption outright.

Now, looking to control its population’s growing dependence on
methamphetamines, Thailand is attempting to legalize kratom, which
it had originally banned 70 years ago.

At the same time, researchers are studying kratom’s ability to
help wean addicts from much stronger drugs, such as heroin and
cocaine. Studies show that a compound found in the plant could even
serve as the basis for an alternative to methadone in treating
addictions to opioids. The moves are just the latest step in
kratom’s strange journey from home-brewed stimulant to illegal
painkiller to, possibly, a withdrawal-free treatment for opioid
abuse.

With kratom’s legal status under review in Thailand and U.S.
researchers delving into the substance’s potential to help drug
addicts, Scientific American spoke with Edward Boyer, a professor
of emergency medicine and director of medical toxicology at the
University of Massachusetts Medical School. Boyer has worked with
Chris McCurdy, a University of Mississippi professor of medicinal
chemistry and pharmacology, and others for the past several years
to better understand whether kratom use should be stigmatized or
celebrated.

[An edited transcript of the interview follows.]

How did you become interested in studying kratom?
A few years ago [the National Institutes of Health] wanted me to do
a bit of consulting on emerging drugs that people might abuse. I
came across kratom while searching online, but didn’t think much of
it at first. When I mentioned it to the NIH, they suggested I speak
with a researcher at the University of Mississippi who was doing
work on kratom. [The researcher, McCurdy,] assured me that kratom
was fascinating, and he started to go through the science behind
it. I decided I needed to look into it further. Talk about chance
favoring the prepared mind. I no sooner hung up the phone when a
case of kratom abuse popped up at Massachusetts General
Hospital.

How did this Mass General patient come to abuse
kratom?
He was a [43-year-old] successful software engineer who had been
self-medicating for chronic pain [as a result of thoracic outlet
syndrome, a group of disorders that occurs when the blood vessels
or nerves in the space between the collarbone and the first rib—the
thoracic outlet—become compressed, causing pain in the shoulders
and neck as well as numbness in the fingers]. He had started with
pain pills, then switched to OxyContin, and then moved to Dilaudid,
which is a high-potency opioid analgesic. He had gotten to the
point where he was injecting himself with 10 milligrams of Dilaudid
per day, which is a large dose. His wife found out and demanded
that he quit.

He read about kratom online and started making a tea out of it.
For the most part, this helped him avoid the opioid withdrawal he
had been experiencing. After he started drinking the kratom tea, he
also began to notice that he could work longer hours and that he
was more attentive to his wife when they would speak. He began
experimenting with ways to boost his alertness by adding modafinil
[a U.S. Food and Drug Administration–approved stimulant] with his
kratom tea. That’s when he started to seize and had to be brought
to the hospital. I have no idea how that combination of drugs
caused a seizure, but that’s how he ended up at Mass General
Hospital. Nobody there had heard of kratom abuse at the time.
[Boyer and several colleagues, including McCurdy, published a case
study about this incident in the June 2008 issue of the journal
Addiction.]

The patient was spending $15,000 annually on kratom, according
to your study, which is quite a lot for tea. What happened when he
left the hospital and stopped using it?
After his stay at Mass General, he went off kratom cold turkey. The
fascinating thing is that his only withdrawal symptom was a runny
noise. As for his opioid withdrawal, we learned that kratom blunts
that process awfully, awfully well.

Where did your kratom research go from there?
I had a small grant from the NIH’s National Institute on Drug Abuse
to look at individuals who self-treated chronic pain with opioid
analgesics they purchased without prescription on the Internet.
This was an extremely restricted population, but it nonetheless
measures in the hundreds of thousands of people. About the time I
started the study, the DEA and the state boards of pharmacy began
shutting down online pharmacies, so sources of pain pills for these
hundreds of thousands of people in the United States dried up
instantaneously. A number of them switched to kratom.

How many people are using kratom in the U.S.?
I don’t know that there’s any epidemiology to inform that in an
honest way. The typical drug abuse metrics don’t exist. But what I
can tell you, based on my experience researching emerging drugs of
abuse is that it is not difficult to get online.

How does kratom work?
Its pharmacology and toxicology aren’t well understood.
Mitragynine—the isolated natural product in kratom leaves—binds to
the same mu-opioid receptor as morphine, which explains why it
treats pain. It’s got kappa-opioid receptor activity as well, and
it’s also got adrenergic activity as well, so you stay alert
throughout the day. This would explain why the guy who overdosed
described himself as being more attentive. Some opioid medicinal
chemists would suggest that kratom pharmacology might [reduce
cravings for opioids] while at the same time providing pain relief.
I don’t know how realistic that is in humans who take the drug, but
that’s what some medicinal chemists would seem to suggest.

Kratom also has serotonergic activity, too—it binds with
serotonin receptors. So if you want to treat depression, if you
want to treat opioid pain, if you want to treat sleepiness, this
[compound] really puts it all together.

Overdosing and drug mixing aside, is kratom
dangerous?
People are afraid of opioid analgesics because they can lead to
respiratory depression [difficulty breathing]. When you overdose on
these drugs, your respiratory rate drops to zero. In animal studies
where rats were given mitragynine, those rats had no respiratory
depression. This opens the possibility of someday developing a pain
medication as effective as morphine but without the risk of
accidentally overdosing and dying.

What barriers have you run into when trying to study
kratom?
I tried to get an NIH grant to study kratom specifically. When I
went to the National Institute on Drug Abuse, they said they’d
never heard of that drug. When I went to the National Center for
Complementary and Alternative Medicine, they said this is a drug of
abuse, and we don’t fund drug of abuse research. They want drugs
that are used therapeutically. [A team led by McCurdy, who confirms
that it is difficult to get funding to study kratom, did manage to
secure a three-year grant from the NIH Centers of Biomedical
Research Excellence to investigate the herb’s opioid-like
effects.]

So the study of this type of substance falls to academics or
pharma companies. Drug companies are the ones who can isolate a
particular compound, do chemistry on it, study and modify the
structure, figure out its activity relationships, and then create
modified molecules for testing. Then you have eventually file for a
new drug application with the FDA in order to conduct clinical
trials. Based on my experiences, the likelihood of that happening
is reasonably small.

Why wouldn’t large pharmaceutical companies try to make a
blockbuster drug from kratom?
At least one pharma company [Smith, Kline & French, now part of
GlaxoSmithKline] was looking at it in the 1960s, but something
didn’t work for them. Either it wasn’t a strong enough analgesic or
the solubility was bad or they didn’t have a drug delivery system
for it. To the state of the art pharmaceutical business thinking in
1960s, this compound was not sufficient to be brought to market. Of
course, now that we have a country with many addicted people dying
of respiratory depression, having a drug that can effectively treat
your pain with no respiratory depression, I think that’s pretty
cool. It might be worth a second look for pharma companies.

There are reports that Thailand might legalize kratom to help
that country control its meth problem. Could that work?
They can decriminalize kratom until they’re blue in the face but
the reality is that kratom is indigenous to Thailand—it’s readily
available and always has been. Yet drug users are still opting for
methamphetamines, which are stronger than kratom, not to mention
dirt cheap and widely available. I suspect that Thailand is just
trying to say that they’re doing something about their meth
problem, but that it might not be that effective.

We examined the use of Kratom (Mitragyna sp.), a dietary supplement with
mu-opioid agonist activity, by members of a cybercommunity who
self-treat chronic pain with opioid analgesics from Internet
pharmacies. Within one year, an increase in the number of mentions
on Drugbuyers.com, a Web site that facilitates the online purchase
of opioid analgesics, suggested that members began managing opioid
withdrawal with Kratom. This study demonstrates the rapidity with
which information on psychoactive substances disseminates through
online communities and suggests that online surveillance may be
important to the generation of effective opioid analgesic abuse
prevention strategies. (Am J Addict 2007;16:352–356)

Recent increases in the use of opioid analgesics (e.g.,
hydrocodone and oxycodone, among others) may represent an expanded
pathway to opioid addiction that is driven, in part, by new sources
of access to these drugs.1,2 Internet pharmacies, which sell drugs
to anyone who can afford to pay, are theorized to increase the
availability of opioid analgesic agents as well as the risk of
opioid abuse and addiction.1,3 As part of ongoing research
examining the relationship between Internet pharmacies and
substance abuse, we have identified several ‘‘pharmacy watch’’ Web
sites.3,4 One, www.drugbuyers.com, not only facilitates the
purchase of pharmaceuticals from Internet pharmacies, but also
serves as a resource through which information on the
self-treatment of chronic pain is disseminated among members. Much
of information exchanged on Drugbuyers relates to sources of opioid
analgesics, tolerance to opioids, and management of withdrawal
using opioid replacement therapy or herbal products. One such
herbal product is Kratom (Mitragyna speciosa Korth), a tree native
to southeast Asia and Africa.5 Mitragynine, the most prevalent
alkaloid isolated from Kratom, and its congeners possess agonist
activity at mu- and delta-opioid receptors and are responsible for
the drug’s opioid-like effects.6–8 Additional animal studies
suggest that mitragynine, a non-opioid indole alkaloid, may also
stimulate post-synaptic alpha-2 adrenergic receptors and=or
antagonize stimulation of 5-HT2A receptors.9 Kratom was
traditionally used in Thailand and Malaysia by manual laborers to
enhance productivity and for its euphoric effects; its indication
for treatment of pain and opium withdrawal was described as early
as 1897.5,10 Kratom is sold by many Internet vendors, suggesting
extensive demand for this product.11 After identifying the use of
Kratom by Drugbuyer’s members, we investigated the ways in which
Drugbuyer’s members incorporated this herb into existing patterns
of opioid analgesic use.

METHODS

We constructed a dataset of Kratom mentions from postings
generated by the 113,000 members of Drugbuyers. com.4 Individuals
join Drugbuyer’s because they procure pharmaceuticals from online
pharmacies; because members purchase medications to treat chronic
conditions, membership on Drugbuyer’s is thought to be stable.4
Among Drugbuyers members, 90% self-treat (e.g., without physician
oversight) chronic pain with opioid analgesics. Up to 925 unique
individuals visit Drugbuyers at any one time, with an average of 22
minutes spent on the Web site per visit.4 The average age of
Drugbuyer’s members is 38 (range: 18–67); 59% are female.4 Members
post an average of 0.5–1.0 messages per minute on the Web site’s
forums. We used the Drugbuyers.com internal search function to
identify each instance where Kratom was mentioned on Web site
forums (‘‘mentions’’) over a one-year period. Mentions are
contained within threads, or series of messages posted as replies
to one another; we identified the initial post on every thread that
mentioned Kratom. We abstracted the initial post, removed all
identifiers such as Drugbuyer’s boardname, and placed all posts in
random order prior to review. Because postings on Drugbuyer’s
forums were made anonymously and with no expectation of privacy,
our Institutional Review Board concluded that this study was
excluded from review. The dataset used in this study was empiric
and was intended to provide preliminary information on the reasons
for which Drugbuyer’s members used Kratom. We analyzed the study
variable using Kappa and descriptive statistics. We used an
abstraction form to collect information about Kratom use. By means
of simple, dichotomous answers (‘‘agree=disagree’’), examiners
assessed the intent underlying Kratom use described in the initial
post. Masked versions were coded independently by two examiners
trained in the use of the form, working according to an instruction
manual, and blinded to results until all data collection was
complete. We determined, using the Kappa statistic, the degree of
interobserver agreement between coders.

RESULTS

The period between November 1, 2004, and October 31, 2005, saw a
dramatic increase in the number of Kratom mentions on Drugbuyers
(see Figure 1). We identified 170 topic threads describing sources
of Kratom (including 38 Internet
vendors primarily from the United States, United Kingdom,
Netherlands, and France), promotions from Web sites selling the
herb, and online introductions to new forum participants. In
addition, 72 total threads (42%) contained information on the
pharmacology, dosing, and route of administration of Kratom.
Twenty-seven threads described indications for Kratom; selected
themes related to Kratom use are presented in Table 1. While a
single thread described using Kratom as a stimulant and as an
antidepressant, members overwhelmingly used Kratom for
self-treatment of withdrawal from opioid analgesic agents.4 Despite
the subjective nature of the study, there was a substantial
agreement between coders (K ¼ 0.65, bias index 0.03, prevalence
0.88).

DISCUSSION

These data suggest striking increases in the use of Kratom to
modulate opioid withdrawal by individuals who procure opioid
analgesic agents from Internet pharmacies. A large proportion of
Drugbuyer’s members self-treat chronic pain without physician
supervision; the appropriation of responsibility for chronic pain
management suggests that Drugbuyer’s members are committed to
using, not quitting, opioids. At the same time, members distinguish
themselves from addicts because drugs improve their ability to
function rather than limit it.4 Because they patronize Internet
pharmacies but shun physicians, pain clinics, and drug treatment
centers, Drugbuyer’s members lie at the intersection of pain
treatment and paths to abuse and addiction.4 To ameliorate the
social and economic costs of chronic opioid analgesic abuse,
Drugbuyer’s members take medication ‘‘holidays’’, or temporary
periods of intentional abstinence, that are intended to decrease
opioid tolerance as well as the cost of treatment once opioid
therapy is resumed. At $10 to $40 per ounce of plant material (and
a recommended dose of 1–8 grams), Kratom is an economical
alternative to established opioid replacement therapies such as
buprenorphine that are available from Internet pharmacies.12,13
Interestingly, the upsurge in mentions coincided with a 2005 U.S.
National Drug Intelligence Center report describing potential
applications for Kratom, including treatment of opioid
withdrawal.11 The increased use of Kratom has led to its being
listed as a drug of concern by the U.S. Drug Enforcement
Administration. This exploratory study provides preliminary
information on reasons for which Kratom is used; it does not,
however, explain why some Drugbuyer’s members select a home remedy
for opioid withdrawal in lieu of formal drug treatment programs.
This preference may reflect the increasing interest in alternative
therapies such as dietary supplements, herbal products, and others
for chronic medical problems.14,15 Alternatively, Drugbuyer’s
members may feel that their opioid use is not problematic, or that
drug treatment is reserved for users of illicit substances. 4 In
this vulnerable population, the utilization of and barriers to
formal drug treatment, as well as the reasons for which pain
treatment and addiction management clinicians have failed to engage
members of this community, are unknown. This study highlights the
potential of the Web as a tool for identifying emerging drug
practices in hidden populations. Proposals that the systematic
assessment of first-person reports of drug use episodes from online
drug encyclopedias (e.g., ‘‘trip reports’’ on http://www.erowid. org) could identify
sentinel drug use events have not borne fruit.16 For a number of
reasons (e.g., a fraction of the trip reports submitted to online
encyclopedias are selected for release, Webmasters stop releasing
reports related to some common drugs, and submissions are edited by
the Web site staff), online encyclopedias cannot provide systematic
surveillance data on drug use behaviors. 17 Because submissions to
Web sites such as Drugbuyers.com are automatically entered and
undergo no screening, these messages offer a real-time glimpse at
the drug-taking behaviors of the community populating that forum.
Furthermore, the use of boardnames (a unique moniker by which
individuals are known to the online community) on webforums confers
additional advantages for drug use surveillance. For example,
specific individuals who introduce new drug use information and
behaviors to the online population can be identified. Because these
persons may serve as opinion leaders for the virtual community,
their effect on drug use knowledge, attitudes, and behaviors of the
online population can be assessed. The dissemination of drug use
information, as well as changes in drug use behavior, can,
therefore, be tracked through social networks of Web-based drug
users. We recognize that our data are preliminary and our study
population is selective. Nonetheless, these findings raise
important questions regarding the impact of the Internet on drug
abuse behaviors of distinct populations. Understanding the
relationship between online pharmacies, chronic pain, and
Internet-based information on treatment for opioid withdrawal may
be important to the generation of effective opioid analgesic abuse
prevention strategies for maturing adults who suffer from chronic
pain. Additional research in this area is urgently needed.

This research was supported by grant R21DA22677 from the
National Institutes of Health, Bethesda, Md (Dr. Boyer).

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